Ethylamine → N-Ethyl-2-[2-(7-methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamide

HRID 1189027Notes

Reaction equation

HRID 1189027 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:21][C:22]2[CH:23]=[N:24][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:26][CH:27]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18](O)=[O:19])[CH2:15][N:16]=1)=[CH:8]2.Cl.[CH2:33]([N:35]=C=NCCCN(C)C)[CH3:34].ON1C2C=CC=CC=2N=N1.C(N)C>O.CN(C)C=O>[CH2:33]([NH:35][C:18](=[O:19])[CH2:17][CH:14]1[S:13][C:12]([C:9]2[NH:10][C:11]3[C:7]([CH:8]=2)=[CH:6][C:5]([O:21][C:22]2[CH:23]=[N:24][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:26][CH:27]=2)=[CH:4][C:3]=3[O:2][CH3:1])=[N:16][CH2:15]1)[CH3:34]

Participants

7

Reactant 4

HCID 6341EthylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67118501[2-(7-Methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid

Product 1

HCID 67118538N-Ethyl-2-[2-(7-methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamideYield 62%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of [2-(7-methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (200 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (120 mg), 1-hydroxybenzotriazole (90 mg) and N,N-dimethylformamide (3 mL) was stirred at room temperature for 30 min, and then ethylamine (2M solution in tetrahydrofuran, 0.43 mL) was added to the mixture. The whole was stirred at room temperature for 15 h. Water was added to the mixture and the resultant was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and brine, dried (MgSO4), filtered, and concentrated in vacuo. The residual crystals were washed with ethyl acetate-hexane and collected by filtration to give pale yellow crystals. The crystals were recrystallized from acetone-methanol to give the title compound (130 mg, 62%) as colorless prisms. MS 489 (MH+). mp 236-237° C.

Workup

  1. stirringThe whole was stirred at room temperature for 15 h
  2. extractionthe resultant was extracted with ethyl acetate
  3. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washThe residual crystals were washed with ethyl acetate-hexane
  8. filtrationcollected by filtration
  9. customto give pale yellow crystals
  10. customThe crystals were recrystallized from acetone-methanol

Sources & evidence

ORD record
ord-cc6ab2736c554e10957fe22da4b6f4d1
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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